High Turnover Among State Health Officials/Public Health Directors: Implications for the Public's Health

State health officials (SHOs) serve a critical role as the leaders of state public health systems. Despite their many responsibilities, there is no formal process for preparation to become an SHO, and few requirements influence the selection of an SHO. Furthermore, to date, no studies have examined SHO tenure or their experiences

Loss of Insulin Receptor in Osteoprogenitor Cells Impairs Structural Strength of Bone

Type 1 diabetes mellitus (T1D) is associated with decreased bone mineral density, a deficit in bone structure, and subsequently an increased risk of fragility fracture. These clinical observations, paralleled by animal models of T1D, suggest that the insulinopenia of T1D has a deleterious effect on bone. To further examine the action of insulin signaling on bone development, we generated mice with an osteoprogenitor-selective (osterix-Cre) ablation of the insulin receptor (IR), designated OIRKO. OIRKO mice exhibited an 80% decrease in IR in osteoblasts. Prenatal elimination of IR did not affect fetal survival or gross morphology. However, loss of IR in mouse osteoblasts resulted in a postnatal growth-constricted phenotype. By 10–12 weeks of age, femurs of OIRKO mice were more slender, with a thinner diaphyseal cortex and, consequently, a decrease in whole bone strength when subjected to bending. In male mice alone, decreased metaphyseal trabecular bone, with thinner and more rodlike trabeculae, was also observed. OIRKO mice did not, however, exhibit abnormal glucose tolerance. The skeletal phenotype of the OIRKO mouse appeared more severe than that of previously reported bone-specific IR knockdown models, and confirms that insulin receptor expression in osteoblasts is critically important for proper bone development and maintenance of structural integrity

Dysregulation of the Intrarenal Vitamin D Endocytic Pathway in a Nephropathy-Prone Mouse Model of Type 1 Diabetes

Microalbuminuria in humans with Type 1 diabetes (T1D) is associated with increased urinary excretion of megalin, as well as many megalin ligands, including vitamin-D-binding protein (VDBP). We examined the DBA/2J diabetic mouse, nephropathy prone model, to determine if megalin and VDBP excretion coincide with the development of diabetic nephropathy. Megalin, VDBP, and 25-hydroxy-vitamin D (25-OHD) were measured in urine, and genes involved in vitamin D metabolism were assessed in renal tissues from diabetic and control mice at 10, 15, and 18 weeks following the onset of diabetes. Megalin, VDBP, and 25-OHD were increased in the urine of diabetic mice. 1-α hydroxylase (CYP27B1) mRNA in the kidney was persistently increased in diabetic mice, as were several vitamin D-target genes. These studies show that intrarenal vitamin D handling is altered in the diabetic kidney, and they suggest that in T1D, urinary losses of VDBP may portend risk for intrarenal and extrarenal vitamin D deficiencies

The Impact of SGLT2 Inhibitors, Compared with Insulin, on Diabetic Bone Disease in a Mouse Model of Type 1 Diabetes

Skeletal co-morbidities in type 1 diabetes include an increased risk for fracture and delayed fracture healing, which are intertwined with disease duration and the presence of other diabetic complications. As such, chronic hyperglycemia is undoubtedly a major contributor to these outcomes, despite standard insulin-replacement therapy. Therefore, using the streptozotocin (STZ)-induced model of hypoinsulinemic hyperglycemia in DBA/2J male mice, we compared the effects of two glucose lowering therapies on the fracture resistance of bone and markers of bone turnover. Twelve week-old diabetic (DM) mice were treated for 9 weeks with: 1) oral canagliflozin (CANA, dose range ~10-16 mg/kg/day), an inhibitor of the renal sodium-dependent glucose co-transporter type 2 (SGLT2); 2) subcutaneous insulin, via minipump (INS, 0.125 units/day); 3) co-therapy (CANA + INS); or 4) no treatment (STZ, without therapy). These groups were also compared to non-diabetic control groups. Untreated diabetic mice experienced increased bone resorption and significant deficits in cortical and trabecular bone that contributed to structural weakness of the femur mid-shaft and the lumbar vertebra, as determined by three-point bending and compression tests, respectively. Treatment with either canagliflozin or insulin alone only partially rectified hyperglycemia and the diabetic bone phenotype. However, when used in combination, normalization of glycemic control was achieved, and a prevention of the DM-related deterioration in bone microarchitecture and bone strength occurred, due to additive effects of canagliflozin and insulin. Nevertheless, CANA-treated mice, whether diabetic or non-diabetic, demonstrated an increase in urinary calcium loss; FGF23 was also increased in CANA-treated DM mice. These findings could herald ongoing bone mineral losses following CANA exposure, suggesting that certain CANA-induced skeletal consequences might detract from therapeutic improvements in glycemic control, as they relate to diabetic bone disease

SGLT2 Inhibitor Therapy Improves Blood Glucose but Does Not Prevent Diabetic Bone Disease in Diabetic DBA/2J Male Mice

Persons with type 1 and type 2 diabetes have increased fracture risk, attributed to deficits in the microarchitecture and strength of diabetic bone, thought to be mediated, in part, by the consequences of chronic hyperglycemia. Therefore, to examine the effects of a glucose-lowering SGLT2 inhibitor on blood glucose (BG) and bone homeostasis in a model of diabetic bone disease, male DBA/2J mice with or without streptozotocin (STZ)-induced hyperglycemia were fed chow containing the SGLT2 inhibitor, canagliflozin (CANA), or chow without drug, for 10 weeks of therapy. Thereafter, serum bone biomarkers were measured, fracture resistance of cortical bone was assessed by μCT analysis and a three-point bending test of the femur, and vertebral bone strength was determined by compression testing. In the femur metaphysis and L6 vertebra, long-term diabetes (DM) induced deficits in trabecular bone microarchitecture. In the femur diaphysis, a decrease in cortical bone area, cortical thickness and minimal moment of inertia occurred in DM (p \u3c 0.0001, for all) while cortical porosity was increased (p \u3c 0.0001). These DM changes were associated with reduced fracture resistance (decreased material strength and toughness; decreased structural strength and rigidity; p \u3c 0.001 for all). Significant increases in PTH (p \u3c 0.0001), RatLAPs (p = 0.0002), and urine calcium concentration (p \u3c 0.0001) were also seen in DM. Canagliflozin treatment improved BG in DM mice by ~35%, but did not improve microarchitectural parameters. Instead, in canagliflozin-treated diabetic mice, a further increase in RatLAPs was evident, possibly suggesting a drug-related intensification of bone resorption. Additionally, detrimental metaphyseal changes were noted in canagliflozin-treated control mice. Hence, diabetic bone disease was not favorably affected by canagliflozin treatment, perhaps due to insufficient glycemic improvement. Instead, in control mice, long-term exposure to SGLT2 inhibition was associated with adverse effects on the trabecular compartment of bone

Freshwater transport in the coupled ocean-atmosphere system: a passive ocean

Conservation of water demands that meridional ocean and atmosphere freshwater transports (FWT) are of equal magnitude but opposite in direction. This suggests that the atmospheric FWT and its associated latent heat (LH) transport could be thought of as a \textquotedblleft coupled ocean/atmosphere mode\textquotedblright. But what is the true nature of this coupling? Is the ocean passive or active? Here we analyze a series of simulations with a coupled ocean-atmosphere-sea ice model employing highly idealized geometries but with markedly different coupled climates and patterns of ocean circulation. Exploiting streamfunctions in specific humidity coordinates for the atmosphere and salt coordinates for the ocean to represent FWT in their respective medium, we find that atmospheric FWT/LH transport is essentially independent of the ocean state. Ocean circulation and salinity distribution adjust to achieve a return freshwater pathway demanded of them by the atmosphere. So, although ocean and atmosphere FWTs are indeed coupled by mass conservation, the ocean is a passive component acting as a reservoir of freshwater

Adaptations of Avian Flu Virus Are a Cause for Concern

We are in the midst of a revolutionary period in the life sciences. Technological capabilities have dramatically expanded, we have a much improved understanding of the complex biology of selected microorganisms, and we have a much improved ability to manipulate microbial genomes. With this has come unprecedented potential for better control of infectious diseases and significant societal benefit. However, there is also a growing risk that the same science will be deliberately misused and that the consequences could be catastrophic. Efforts to describe or define life-sciences research of particular concern have focused on the possibility that knowledge or products derived from such research, or new technologies, could be directly misapplied with a sufficiently broad scope to affect national or global security. Research that might greatly enhance the harm caused by microbial pathogens has been of special concern (1–3). Until now, these efforts have suffered from a lack of specificity and a paucity of concrete examples of “dual use research of concern” (3). Dual use is defined as research that could be used for good or bad purposes. We are now confronted by a potent, real-world example

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Global Oceans

Global Oceans is one chapter from the State of the Climate in 2019 annual report and is avail-able from https://doi.org/10.1175/BAMS-D-20-0105.1. Compiled by NOAA’s National Centers for Environmental Information, State of the Climate in 2019 is based on contr1ibutions from scien-tists from around the world. It provides a detailed update on global climate indicators, notable weather events, and other data collected by environmental monitoring stations and instru-ments located on land, water, ice, and in space. The full report is available from https://doi.org /10.1175/2020BAMSStateoftheClimate.1

Ownership identity, strategy and performance:business group affiliates versus independent firms in India

We consider whether the impact of entrepreneurial orientation on business performance is moderated by the company affiliation with business groups. Within business groups, we explore the trade-off between inter-firm insurance that enables risk-taking, and inefficient resource allocation. Risk-taking in group affiliated firms leads to higher performance, compared to independent firms, but the impact of proactivity is attenuated. Utilizing Indian data, we show that risk-taking may undermine rather than improve business performance, but this effect is not present in business groups. Proactivity enhances performance, but less so in business groups. Firms can also enhance performance by technological knowledge acquisition, but these effects are not significantly different for various ownership categories